PURPOSE: Whole-body heat stress compromises the control of blood pressure during an orthostatic challenge, although the extent to which this occurs can vary greatly between individuals. The mechanism(s) responsible for these varying responses remain unclear. This study tested the hypothesis that the individuals who are best able to tolerate an orthostatic challenge while heat stressed are the ones with the largest increase in sympathetic activity during orthostasis, indexed from recordings of muscle sympathetic nerve activity (MSNA).METHODS: MSNA, arterial blood pressure, and heart rate were recorded from 11 healthy volunteers throughout passive whole-body heating and during 15 min of 60° head-up tilt (HUT) or until the onset of pre-syncopal symptoms.RESULTS: Whole-body heating significantly increased core temperature (~0.9°C), supine heart rate and MSNA. Eight of 11 subjects developed pre-syncopal symptoms resulting in early termination of HUT. The HUT tolerance time was positively correlated (R = 0.82, P = 0.01) with the increase in MSNA by HUT.CONCLUSION: These data suggest that the individuals with the largest increase in MSNA during upright tilt have the greatest capacity to withstand the orthostatic challenge while heat stressed.